EP0116238A1 - Compositions thérapeutiques et leur application pour améliorer la fonction cérébrale - Google Patents
Compositions thérapeutiques et leur application pour améliorer la fonction cérébrale Download PDFInfo
- Publication number
- EP0116238A1 EP0116238A1 EP19830308041 EP83308041A EP0116238A1 EP 0116238 A1 EP0116238 A1 EP 0116238A1 EP 19830308041 EP19830308041 EP 19830308041 EP 83308041 A EP83308041 A EP 83308041A EP 0116238 A1 EP0116238 A1 EP 0116238A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- piracetam
- analog
- human
- deanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 230000002708 enhancing effect Effects 0.000 title claims abstract description 11
- 230000003925 brain function Effects 0.000 title claims abstract description 9
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 5
- 239000000203 mixture Substances 0.000 title claims description 16
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical class NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims abstract description 29
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229960001231 choline Drugs 0.000 claims abstract description 19
- 210000004556 brain Anatomy 0.000 claims abstract description 16
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229960004373 acetylcholine Drugs 0.000 claims abstract description 15
- 210000002569 neuron Anatomy 0.000 claims abstract description 9
- 238000010304 firing Methods 0.000 claims abstract description 7
- 230000000779 depleting effect Effects 0.000 claims abstract description 5
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 claims description 22
- 229960002887 deanol Drugs 0.000 claims description 21
- 229960004526 piracetam Drugs 0.000 claims description 9
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 claims description 5
- 229960001697 physostigmine Drugs 0.000 claims description 5
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical group C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 claims description 5
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 claims description 4
- HPHUVLMMVZITSG-UHFFFAOYSA-N Etiracetam Chemical compound CCC(C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-UHFFFAOYSA-N 0.000 claims description 4
- 229950007353 etiracetam Drugs 0.000 claims description 4
- 229960001227 oxiracetam Drugs 0.000 claims description 4
- IHLAQQPQKRMGSS-UHFFFAOYSA-N oxiracetam Chemical compound NC(=O)CN1CC(O)CC1=O IHLAQQPQKRMGSS-UHFFFAOYSA-N 0.000 claims description 4
- 229960003389 pramiracetam Drugs 0.000 claims description 4
- ZULJGOSFKWFVRX-UHFFFAOYSA-N pramiracetam Chemical compound CC(C)N(C(C)C)CCNC(=O)CN1CCCC1=O ZULJGOSFKWFVRX-UHFFFAOYSA-N 0.000 claims description 4
- XZTYGFHCIAKPGJ-UHFFFAOYSA-N Meclofenoxate Chemical compound CN(C)CCOC(=O)COC1=CC=C(Cl)C=C1 XZTYGFHCIAKPGJ-UHFFFAOYSA-N 0.000 claims description 3
- 229960000793 aniracetam Drugs 0.000 claims description 3
- ZXNRTKGTQJPIJK-UHFFFAOYSA-N aniracetam Chemical compound C1=CC(OC)=CC=C1C(=O)N1C(=O)CCC1 ZXNRTKGTQJPIJK-UHFFFAOYSA-N 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 229960003442 meclofenoxate Drugs 0.000 claims description 3
- 229960003295 pirisudanol Drugs 0.000 claims description 3
- KTOAWCPDBUCJED-UHFFFAOYSA-N pirisudanol Chemical compound CN(C)CCOC(=O)CCC(=O)OCC1=CN=C(C)C(O)=C1CO KTOAWCPDBUCJED-UHFFFAOYSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims 2
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 3
- 230000001713 cholinergic effect Effects 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- -1 e.g. Chemical compound 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
- 0 *N(CCC1)C1=O Chemical compound *N(CCC1)C1=O 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 239000004381 Choline salt Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- SUHOQUVVVLNYQR-MRVPVSSYSA-N choline alfoscerate Chemical compound C[N+](C)(C)CCOP([O-])(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-N 0.000 description 1
- 235000019417 choline salt Nutrition 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
Definitions
- This invention relates to brain-function enhancing compositions.
- Various drugs are known for the treatment of medical disorders affecting acetylcholine-containing neurons in the brain.
- One such drug, piracetam has been administered alone and, as is described in Growdon et al. U.S. Patent No. 4,355,927, in combination with choline, choline salts, "or a compound that dissociates to choline, such as an acylglycerophosphocholine, e.g., lecithin, lysolecithin, [or] glycerophosphatidyl choline.”
- Piracetam has the following structure:
- piracetam A number of analogs of piracetam which, like piracetam, are capable of enhancing the firing of acetylcholine-containing brain neurons in a human, while depleting brain acetylcholine level.
- oxiracetam having the structure:
- Oxiracetam is described in Itil et al. (1982) Drug Development Research 2, 447.
- pramiracetam (usually provided in the form of the hydrochloride), having the structure: Pramiracetam is described in British Pat. No. 1,588,082.
- the invention features enhancing brain function in a human by administering to the human an effective amount of a piracetam analog capable of enhancing firing of acetylcholine-containing brain neurons in a human while depleting the brain acetylcholine level in the human, and an effective amount of a second compound capable of slowing the rate of choline depletion in the human.
- the second compound is present in an amount effective to slow choline depletion to a degree sufficient to counteract the acetylcholine depletion caused by the piracetam analog; i.e., to prevent the piracetam analog from bringing about a net decrease in brain acetylcholine.
- the piracetam analog is piracetam, aniracetam, pramiracetam, etiracetam, or oxiracetam; and the second compound is deanol or a compound which dissociates to form deanol, e.g., a salt or ester of deanol, e.g., meclofenoxate or pyrisuccideanol.
- the second compound is an acetylcholine esterase inhibitor, e.g. physostigmine.
- Two such second compounds can be used together, e.g., deanol and physostigmine can be used together.
- deanol and physostigmine can be used together.
- the advantage of such use is that, for example, when deanol and physostigmine are both used, lower amounts of each can be used; this is particularly advantageous in the case of physostigmine, which is toxic in large doses.
- the invention provides the brain function enhancement of piracetam analogs without the disadvantages associated with these.
- Piracetam analogs work by enhancing firing of brain neurons.
- This firing enhancement can deplete brain acetylcholine levels, thereby producing, in one reppect, an effect deleterious to brain function.
- this deleterious effect is counteracted by a compound capable of slowing the rate of choline depletion; e.g., deanol, which inhibits choline metabolism.
- the preferred therapeutic composition contains piracetam and deanol or a compound which dissociates to form deanol.
- piracetam and.deanol are commercially available, as are deanol esters and salts such as meclofenoxate (Fr. Pat. M398) and pyrisuccideanol (German Pat. No. 2,102,831).
- the piracetam analog and the second compound can each be administered alone or in combination with a pharmaceutically acceptable carrier, or the active agents and carrier can be combined.
- compositions can be provided in the form of capsules or tablets, either ordinary or time-release.
- the compositions can also take the form of ingestible liquid, e.g., syrup, or an injectible liquid.
- the piracetam analog can be administered in an amount between 0.1 and 100 mg/kg/day.
- the second compound e.g. deanol or a compound which dissociates to form deanol, can be administered in an amount between 10 and 2,000 mg/kg/day.
- the piracetam analog and second compound rather than beingladministered in one therapeutic composition, can be administered simultaneously or near enough in time to.achieve the desired counteracting effect.
- compositions of the invention When administered to a human (e.g., orally, parenterally, intravenously, or by suppository) can enhance brain function associated with acetylcholine-containing brain neurons.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45580883A | 1983-01-05 | 1983-01-05 | |
| US56135183A | 1983-12-16 | 1983-12-16 | |
| US561351 | 1983-12-16 | ||
| US455808 | 1999-12-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0116238A1 true EP0116238A1 (fr) | 1984-08-22 |
Family
ID=27037995
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP19830308041 Withdrawn EP0116238A1 (fr) | 1983-01-05 | 1983-12-30 | Compositions thérapeutiques et leur application pour améliorer la fonction cérébrale |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0116238A1 (fr) |
| AU (1) | AU2301483A (fr) |
| CA (1) | CA1209047A (fr) |
| GR (1) | GR79143B (fr) |
| MA (1) | MA19994A1 (fr) |
| PT (1) | PT77918A (fr) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2578421A1 (fr) * | 1985-03-05 | 1986-09-12 | Ciba Geigy Ag | Compositions pharmaceutiques utiles pour le traitement des troubles de la memoire |
| US4765985A (en) * | 1985-03-05 | 1988-08-23 | Ciba-Geigy Corporation | Devices and methods for treating memory impairment |
| US4900748A (en) * | 1988-03-04 | 1990-02-13 | The United States Of America As Represented By The Department Of Health And Human Services | Carbamates related to (-)-physostigmine as cholinergic agents |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4355027A (en) * | 1977-11-02 | 1982-10-19 | Massachusetts Institute Of Technology | Process and composition for treating disorders by administering piracetam and choline |
-
1983
- 1983-12-29 GR GR73383A patent/GR79143B/el unknown
- 1983-12-30 AU AU23014/83A patent/AU2301483A/en not_active Abandoned
- 1983-12-30 EP EP19830308041 patent/EP0116238A1/fr not_active Withdrawn
-
1984
- 1984-01-04 PT PT7791884A patent/PT77918A/pt unknown
- 1984-01-04 CA CA000444666A patent/CA1209047A/fr not_active Expired
- 1984-01-04 MA MA20215A patent/MA19994A1/fr unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4355027A (en) * | 1977-11-02 | 1982-10-19 | Massachusetts Institute Of Technology | Process and composition for treating disorders by administering piracetam and choline |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2578421A1 (fr) * | 1985-03-05 | 1986-09-12 | Ciba Geigy Ag | Compositions pharmaceutiques utiles pour le traitement des troubles de la memoire |
| US4765985A (en) * | 1985-03-05 | 1988-08-23 | Ciba-Geigy Corporation | Devices and methods for treating memory impairment |
| US4900748A (en) * | 1988-03-04 | 1990-02-13 | The United States Of America As Represented By The Department Of Health And Human Services | Carbamates related to (-)-physostigmine as cholinergic agents |
Also Published As
| Publication number | Publication date |
|---|---|
| CA1209047A (fr) | 1986-08-05 |
| AU2301483A (en) | 1984-07-12 |
| MA19994A1 (fr) | 1984-10-01 |
| GR79143B (fr) | 1984-10-02 |
| PT77918A (en) | 1984-02-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| AK | Designated contracting states |
Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
| 17P | Request for examination filed |
Effective date: 19840917 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
| 18W | Application withdrawn |
Withdrawal date: 19880323 |
|
| RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: MOREAU, JACQUES-PIERRE |